High drug-loaded microspheres enabled by controlled in-droplet precipitation promote functional recovery after spinal cord injury.
High drug-loaded microspheres enabled by controlled in-droplet precipitation promote functional recovery after spinal cord injury.
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通过控制液滴内沉淀实现高载药微球促进脊髓损伤后的功能恢复
DOI：
10.1038/s41467-022-28787-7
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发表时间：
2022-03-10
影响因子：
16.6
通讯作者：
Liu D
中科院分区：
文献类型：
--
作者：
Li W;Chen J;Zhao S;Huang T;Ying H;Trujillo C;Molinaro G;Zhou Z;Jiang T;Liu W;Li L;Bai Y;Quan P;Ding Y;Hirvonen J;Yin G;Santos HA;Fan J;Liu D
具有高药物含量的药物递送系统可以使赋形剂施用最小化，减少副作用，提高治疗功效和/或促进患者依从性。然而，设计这样的系统是极具挑战性的，因为它们的负载能力固有地受到药物分子和载体材料之间的相容性的限制。为了减轻药物-载体相容性对治疗剂包封的限制，我们开发了顺序固化策略。在这种策略中，精确控制溶剂从液滴中的扩散，确保了在聚合物材料固化之前药物分子的快速液滴内沉淀。在聚合物固化后，大量的药物纳米颗粒嵌入聚合物基质中，形成纳米微结构的微球。所有获得的微球表现出长期储存稳定性，药物分子的控制释放，最重要的是，高质量分数的治疗剂（21.8-63.1重量%）。得益于其高载药量，纳米微结构的缩醛化葡聚糖微球通过单次鞘内注射在有限的给药体积（10 μL）内递送高剂量的甲基强的松龙（400 μg）。缩醛化葡聚糖用量为低载药微球用量的1/433。此外，甲基强的松龙从高载药微球中的控释有助于改善脊髓损伤治疗中的治疗效果和降低副作用，而不是低载药微球和游离药物。
Drug delivery systems with high content of drug can minimize excipients administration, reduce side effects, improve therapeutic efficacy and/or promote patient compliance. However, engineering such systems is extremely challenging, as their loading capacity is inherently limited by the compatibility between drug molecules and carrier materials. To mitigate the drug-carrier compatibility limitation towards therapeutics encapsulation, we developed a sequential solidification strategy. In this strategy, the precisely controlled diffusion of solvents from droplets ensures the fast in-droplet precipitation of drug molecules prior to the solidification of polymer materials. After polymer solidification, a mass of drug nanoparticles is embedded in the polymer matrix, forming a nano-in-micro structured microsphere. All the obtained microspheres exhibit long-term storage stability, controlled release of drug molecules, and most importantly, high mass fraction of therapeutics (21.8–63.1 wt%). Benefiting from their high drug loading degree, the nano-in-micro structured acetalated dextran microspheres deliver a high dose of methylprednisolone (400 μg) within the limited administration volume (10 μL) by one single intrathecal injection. The amount of acetalated dextran used was 1/433 of that of low drug-loaded microspheres. Moreover, the controlled release of methylprednisolone from high drug-loaded microspheres contributes to improved therapeutic efficacy and reduced side effects than low drug-loaded microspheres and free drug in spinal cord injury therapy.
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影响因子：
56.9
作者：
Kalsin, AM;Fialkowski, M;Grzybowski, BA
通讯作者：
Grzybowski, BA
影响因子：
4.6
作者：
Gordillo, JM;Cheng, ZD;Weitz, DA
通讯作者：
Weitz, DA
影响因子：
2.9
作者：
Kuwana, S;Okada, Y;Natsui, T
通讯作者：
Natsui, T
影响因子：
14.5
作者：
Fleming, Jennifer C.;Norenberg, Michael D.;Weaver, Lynne C.
通讯作者：
Weaver, Lynne C.
影响因子：
2.4
作者：
Amstad, Esther;Chen, Xiaoming;Weitz, David A.
通讯作者：
Weitz, David A.